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Little is known about the specific role of histones - the protein ?spool?
around which the famous DNA double helix is folded, January 2005.
Now, researchers at the University of Virginia Health System have
unraveled one mystery about what histones accomplish in the complex chemical
cascade that determines the function of a cell in the body. Their findings
are published in the Jan. 12, 2005 online edition of the journal Nature.
Scientists at U.Va?s Department of Biochemistry and Molecular Genetics
discovered that a previously known protein called Chd1 recognizes a flag (or
code) on histones and physically binds to a certain mark (a methylation
mark.) The protein Chd1 then attracts a huge complex of other proteins,
called SAGA, that can turn genes on in the cell nucleus.
?This is a good example of how proteins respond to the histone code,?
explained study senior author Patrick Grant, PhD, an Assistant Professor of
Biochemistry and Molecular Genetics at U.Va. ?There is a theory, proposed by
Dr David Allis at Rockefeller University and Dr Brian Strahl at the
University of North Carolina , that DNA does not function in isolation.
Rather, its? function can be dictated by this modification of histones,
which can determine whether DNA is exposed and accessible or not. This takes
us one step closer to understanding how chemical information carried on
histones, rather than DNA, is recognized and read during the regulation of
Chd1 mutation has been linked to a rare neurological disease called CHARGE
syndrome that causes birth defects, including eye abnormalities, facial
palsy and swallowing problems, blocked nasal passages, heart defects and
delayed development. Already, Grant and his colleagues are working in the
lab on a project involving the role of SAGA proteins in another rare
neurological disorder called spinal cerebellar ataxia type 7 that causes
neurodegeneration and blindness. Grant believes that Chd1 and SAGA
interaction may be vital for normal brain development and function.
Grant said that, until his discovery, there have been very few proteins
identified that recognize these methylation marks on histones. He said
information has recently emerged about how genes can be turned off by
histone methylation and how abnormal chemical modification of histones may
underlie the formation of certain cancers. ?This research adds important
knowledge to our understanding of how cells signal to turn genes on,? Grant
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